The Impact of SARS-COV-2 on two Colorectal Cancer screening centres.

BowelScreen paused activity in March 2020 to prioritise the response to the COVID-19 pandemic. The aim of this study was to examine the impact of this delay. Cases affected by the pause and subsequently completed were compared to the same period in 2019. Endoscopy and histology data were obtained from the BowelScreen database and patient records. One-hundred and seven colonoscopies were performed during the study period. This compared with 224 colonoscopies during the same period in 2019. Median lead time to colonoscopy in 2020 was 74 days compared to 34 days in 2019. Adenoma detection rate was 59% for both periods. Advanced adenoma and cancer detection rates were similar in both periods. While there was a marked reduction in activity and significant delays for BowelScreen patients during the first wave of the COVID-19 pandemic, this does not appear to have impacted on clinical outcomes for patients who attended for screening colonoscopy.

Age related influence on screening coverage and satisfaction. with CervicalCheck.

The aim of this study was to evaluate levels of satisfaction of women attending the CervicalCheck programme and reasons for the age differential in screening uptake. A questionnaire was sent to 5,000 randomly selected attenders with a normal smear test (3,500 aged 25-44, 1,500 aged 45-60). Almost all in both age groups said they would return to CervicalCheck if invited (98.5%; 98.5%) and recommend the service to family/friend (99.6%; 99.5%). The single independent predictor of 'would recommend to family/friend' was willingness to return to CervicalCheck (OR = 31 (5.2-183.7)). Predictors of 'would return if invited' were knowledge of when due to return (OR = 2.5 (1.3-5.0)) and having contacted or having received a letter of invitation from CervicalCheck (OR = 3.1 (1.6-6.1)). Independent predictors of 'knowledge of when due to return' were older age group (OR = 0.5 (0.4-0.7)) and willingness to return to CervicalCheck (OR = 3.2 (1.2-6.3)). The GP is particularly important in informing older women and encouraging attendance.

Non-pulmonary chronic diseases in adults with cystic fibrosis: analysis of data from the Cystic Fibrosis Registry.

The international literature shows that the demography of cystic fibrosis (CF) is changing, with patients increasingly surviving into adulthood. As they age, patients with CF become more susceptible to specific non-pulmonary chronic diseases. In this study, adult data from the CF Registry of Ireland (CFRI) was used to determine the prevalence and associated features of these diseases. 104 (25.7%) adults had diabetes versus 13 (2.9%) children (p < 0.001). Liver disease was present in 47 (11.6%) adults and 26 (5.7%) children (p = 0.002). 173 (42.7%) adults had bone disease versus 25 (5.5%) children (p < 0.001). Adults with one non-pulmonary chronic disease, for example liver disease, were more likely to have another (p = 0.002), those with diabetes and bone disease had a higher number of hospital admissions in the last 12 months (p < 0.001 for both) and higher rates of depression (p = 0.046 and p = 0.049, respectively). These results highlight a number of challenges for the Irish healthcare system.

Smoking in vehicles is lower than mobile telephone use while driving, but is socially patterned.

Legislation is being considered which bans smoking in cars carrying children under the age of 16. This was an observational survey of smoking by drivers and passengers and mobile phone use by drivers in 2,230 cars over three time periods in two Dublin locations. The observed prevalence of mobile telephone use (2.56%) was higher than smoking (1.39%) (p < 0.01), but was low in both. There was no significant variation according to time of day. There was an inverse pattern according to car value for smoking drivers (p = 0.029). Eight adult passengers and just one child were observed as being exposed to a smoking adult driver. In conclusion, the public health importance of regulating passive smoke exposure is clear but the resources required to police such a ban in vehicles may be labour intensive for the yield in detection or prevention.

General Practitioner referrals to Child and Adolescent Mental Health Services: Did they differ during Covid-19?

OBJECTIVES: The COVID pandemic has been associated with poorer mental health in youth. This study aimed to evaluate any change in General Practitioner (GP) referral pattern to Child and Adolescent Mental Health (CAMH) services during the first 10 months of Covid-19 and compare with a similar time frame in 2019. METHODS: All accepted referrals to a CAMH Service in Dublin during the study time frame were reviewed. Referral letters were batch anonymised and clinical data extracted using a study specific proforma for analysis. RESULTS: Referral numbers between the two time periods did not statistically differ. Proportionally more females were referred during the pandemic, increasing to 56.9%, n = 99, compared to 43.1%, n = 75 in 2019 (p = 0.01). Referrals were more often designated by the clinician as urgent during the pandemic (61.3%, n = 98) than before (39%, n = 62, p < 0.001). Referrals outlining self-harm or suicidal ideation increased significantly, from 42.1% (n = 67) to 55.9% (n = 90) (p = 0.014). Referrals for externalising problems fell from 2019 rates; ADHD (21.4%, n = 34 vs 11.1%, n = 18; p = 0.013), ASD (26.4%, n = 42 vs 16.1%, n = 26; p = 0.038) and conduct problems (23.3%, n = 37 vs 7.4%, n = 12; p < 0.001). Although numbers for psychosis in 2019 were low (10.7%, n = 17), these also fell significantly in 2020 (2.5%, n = 4; p < 0.001). DISCUSSION: The finding of reduced referrals for ADHD and ASD has not previously been reported. With concerns regarding educational loss linked to online learning, it is crucial that these youth are not doubly disadvantaged by delayed referral and education decline.

Provision of smoking cessation support for patients following a diagnosis of cancer in Ireland.

There is growing evidence that smoking cessation (SC) improves outcomes following diagnosis of cancer. Notwithstanding adverse outcomes, a significant number of those diagnosed with cancer continue to smoke. Our objective was to document the SC services provided for patients with cancer by specialist adult cancer hospitals across Ireland, a country with a stated tobacco endgame goal. A cross-sectional survey based on recent national clinical guidelines was used to determine SC care delivery across eight adult cancer specialist hospitals, and one specialist radiotherapy centre. Qualtrics was used. The response rate was 88.9% with data reported from seven cancer hospitals and one specialist radiotherapy centre, all indicating they had some SC related provision (100%). Stop smoking medications were provided to cancer inpatients in two hospitals, at outpatients and attending day ward services in one hospital. Smokers with cancer were referred automatically to the SC service in two hospitals at diagnosis. While stop smoking medications were available 24 h a day in five hospitals, most did not stock all three (Nicotine Replacement Therapy, Bupropion, Varenicline). One hospital advised they had data on uptake of SC services for smokers with cancer but were unable to provide detail. There is considerable variation in SC information and services provided to cancer patients across adult cancer specialist centres in Ireland, reflecting the suboptimal practice of smoking cessation for patients with cancer found in the limited international audits. Such audits are essential to demonstrate service gaps and provide a baseline for service improvement.

Impact of second reminder invitation on uptake of screening and cancer detection in BreastCheck.

This research aims to quantify the impact of reminder invitations on uptake and cancer detection in Ireland. Examination of BreastCheck's clinical database (2000-2010) to determine number of women screened following first invitation and after reminder; comparison by age group and screening phase with outcomes of recall rate, cancer detection and true positive rates. Of 819,182 first invitations sent 448,974 (54.8%) women attended. 245,157 (66.2%) women attended after reminder invitations, increasing uptake by 29.9% to 694,131 (84.7%) and cancers detected by 1,550 (35%). Women awaiting a reminder were less likely recalled for assessment 9,555 (3.9%) than respondents to first invitation 2,887 (4.04%) (p=0.004). Younger, mainly initial women were more likely recalled for assessment after first invitation. There was no difference between cohorts for cancer detection rate or true positive rate. Reminders increased uptake, supporting international evidence. For programme efficiency attendance at first invitation is optimal. For maximum programme effectiveness attendance must be encouraged with reminders.

Experience of discrimination and engagement with mental health and other services by Travellers in Ireland: findings from the All Ireland Traveller Health Study (AITHS).

OBJECTIVES: Irish Travellers are an indigenous ethnic minority population in Ireland, with poor life expectancy. This study aims to identify factors associated with reported discrimination and how this affects their experiences of accessing and quality of health services, including mental health. METHODS: The All Ireland Traveller Health Study was a cross-sectional census study in 2010. All Traveller families completed a survey questionnaire (n = 6540), and at random an adult selected from the family completed either a health status (health status study = 1547) or health services utilisation survey (HSU = 1576). Experience of discrimination (EOD) from the census was analysed in relation to HSU data on services used in the previous 12 months and reported experiences of access and quality of that health service. Census variables were analysed in relation to EOD and perceived discrimination (PD). RESULTS: In the final models, EOD and PD were significantly associated with socio-demographic, socio-cultural and living conditions. The multivariate odds of reporting EOD ranged from OR 1.84 to 2.13 and were significant for those reporting worse opportunities in accessing health services, mental health (p = 0.001), hospitals (p < 0.001) and public health nurses (p < 0.001). The multivariate odds of reporting EOD ranged from OR 1.95 to 2.71 and remained significant for those who reported they had poorer experiences than others when using health services, quality of experience (OR 2.18, p =< 0.001), trust in providers (OR 1.95, p =< 0.001) and appropriate information (OR 2.71, p =< 0.001). CONCLUSIONS: Travellers experience high levels of discrimination which negatively affects their engagement with health services. Culturally competent services need to be developed.

A rapid review of Irish Traveller mental health and suicide: a psychosocial and anthropological perspective.

INTRODUCTION: Irish Travellers are an indigenous ethnic minority (IEM) with poor health outcomes. Whilst they constitute less than 1% of the Irish population, they account for 10% of national young adult male suicide statistics. METHODS: A rapid review of scientific publications related to mental health and suicide in Irish Travellers was undertaken following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches of PubMed, PsycINFO and Google Scholar were performed. Eligibility criteria included: (i) Irish Travellers/Gypsy Travellers; (ii) information on mental health/suicide/self-harm; (iii) psychosocial anthropological perspectives of mental health; (iv) publications in english. Data on studies including design, methods, participants and key findings were extracted using a spreadsheet template. RESULTS: From 5160 scientific references over the past 20 years, 19 papers made reference to Traveller mental health, and only 5 papers made specific data-based reference to suicide in Travellers. It was only when we qualified Travellers as being 'Irish Travellers' in our scientific review did we detect meaningful references to their existence as an IEM, and their health and well-being. Due to sample sizes and heterogeneity in design, results were synthesised narratively. DISCUSSION: This paper draws together strands from the disciplines of psycho/socio/anthropological perspectives to gain deeper insights into mental health and suicide in Irish Travellers. In a knowledge vacuum, it behoves the scientific community to explain the value of scientific research and rigour to both policymakers as well as Travellers, shifting the existing discourse towards new knowledge and understanding around mental health and suicide in Travellers.

Multiple sclerosis prevalence in Ireland: relationship to vitamin D status and HLA genotype.

BACKGROUND: The relationship between prevalence of multiple sclerosis (MS) and latitude may be due to both genetic and environmental factors. The hypothesis that, in Ireland, MS prevalence is increasing and that north-south differences relate to variation in serum 25-hydroxyvitamin D (25(OH)D) levels was tested in this study. PATIENTS AND METHODS: Patients and matched control subjects were identified in counties Donegal, Wexford and South Dublin through multiple sources. Prevalence was determined. Blood samples were taken for serum 25(OH)D and serum intact parathyroid hormone measurement, and DNA was extracted. RESULTS: Prevalence in 2007 was significantly greater in Donegal (northwest) (290.3/105, 95% CI 262.3 to 321.7) compared with 2001 (184.6/105; 162 to 209.5). In Wexford (southeast), there was a non-significant increase in prevalence in 2007 compared with 2001. Prevalence was significantly higher in Donegal than in Wexford (144.8/105; 126.7 to 167.8, p<0.0001) and South Dublin (127.8/105; 111.3 to 148.2, p<0.0001). Overall, mean 25(OH)D levels were low and did not differ between patients (38.6 nmol/l) and controls (36.4 nmol/l) However, significantly more patients than controls had 25(OH)D levels <25 nmol/l (deficiency) (p=0.004). Levels of 25(OH)D (mean 50.74 nmol/l) were significantly higher in South Dublin (area with lowest prevalence) (p<0.0001) than in Donegal or Wexford. HLA DRB1*15 occurred most frequently in Donegal (greatest MS prevalence) and least frequently in South Dublin. CONCLUSION: Vitamin D deficiency is common in Ireland. Latitudinal variation in MS probably relates to an interaction between genetic factors and environment (25(OH)D levels), and MS risk may be modified by vitamin D in genetically susceptible individuals.

The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa.

Lap belt injuries in children.

The use of adult seat belts without booster seats in young children may lead to severe abdominal, lumbar or cervical spine and head and neck injuries. We describe four characteristic cases of lap belt injuries presenting to a tertiary children's hospital over the past year in addition to a review of the current literature. These four cases of spinal cord injury, resulting in significant long-term morbidity in the two survivors and death in one child, arose as a result of lap belt injury. These complex injuries are caused by rapid deceleration characteristic of high impact crashes, resulting in sudden flexion of the upper body around the fixed lap belt, and consequent compression of the abdominal viscera between the lap belt and spine. This report highlights the dangers of using lap belts only without shoulder straps. Age-appropriate child restraint in cars will prevent these injuries.

Delayed cystic fibrosis presentation in children in the absence of newborn screening.

Newborn cystic fibrosis (CF) screening facilitates early diagnosis and nutritional intervention, which prevents malnourishment and improves growth in childhood. To provide baseline information on the natural history of CF in the Republic of Ireland, where newborn screening has not yet been introduced and CF incidence is high (1:1353 live births), we examined the effect of presentation mode, symptom type and gender on age at diagnosis. Median age at diagnosis was calculated by gender and for presentation mode/symptom type for 601 CF registry children diagnosed 1986-2007. Modes of presentation were each significantly associated with delayed presentation. An adjusted odds ratio of 4.5 (95% CI: 1.8, 11.1) was determined for presentation with family history, 43.1 for gastrointestinal symptoms presentation (95% CI: 18.3, 101.4), 96.9 for both respiratory and gastrointestinal symptoms (95% CI: 38.6, 243,4), and 115.4 for respiratory symptoms (95% CI: 45.2, 294.7). Children with respiratory symptoms had the greatest likelihood of delayed diagnosis (median age: 20.4 months), followed by those with respiratory and gastrointestinal symptoms (9.2 months). Gender was not significantly associated with a delayed presentation when presentation mode was taken into account.

Introduction of the low risk ankle rule to a paediatric emergency department.

INTRODUCTION: Ankle injuries are a common presentation to the paediatric emergency department (PED), accounting for approximately 2% of presentations.1 X-rays are ordered for 85-95% of patients but only 12% of x-rays reveal a fracture. Clinical prediction rules, such as The Low Risk Ankle Rule (LRAR) exist to help clinicians safely reduce the frequency of radiography in these injuries. The LRAR has been shown to reduce imaging by up to 60% without missing any clinically significant fractures. We sought to introduce The LRAR into our department and study its outcomes on our practice. AIMS: To introduce the LRAR into our department and study its effects on our radiography rate and length of stay (LOS). METHODS: An audit of x-ray rates in ankle injuries in 2016 was performed to determine our department's baseline rate of radiography and LOS. We then conducted education sessions and created x-ray ordering prompts to encourage clinicians to use the LRAR. We introduced the LRAR, with a pilot period initially, and gathered data prospectively. RESULTS: 969 patients presented in with an ankle injury in 2016, 90.7% of these patients had an x-ray. The median LOS was 109 min. 92 patients presented during  the LRAR implementation period with an ankle injury. Nine patients had exclusion criteria from using the LRAR and the attending physician did not use the LRAR in four patients. Of the remaining 79 patients, 49 had a LRAR positive exam. Only one of these patients went on to have an x-ray, which was normal. The 30 patients with a LRAR negative exam all had an x-ray. Overall, our x-ray rate during the study period was 40/92 (43.4%), a reduction of 47.3%. The average LOS during the study was 101 min. No clinically significant fractures were missed. CONCLUSION: The LRAR can safely and effectively reduce the rate of radiography in ankle injuries, without missing any clinically significant fractures.

Expression of a protease-resistant insulin-like growth factor-binding protein-4 inhibits tumour growth in a murine model of breast cancer.

BACKGROUND: Insulin-like growth factor 1 (IGF1) promotes breast cancer and disease progression. Bioavailability of IGF1 is modulated by IGF-binding proteins (IGFBPs). IGFBP4 inhibits IGF1 activity but cleavage by pregnancy-associated plasma protein-A (PAPP-A) protease releases active IGF1. METHODS: Expression of IGF pathway components and PAPP-A was assessed by western blot or RT-PCR. IGFBP4 (dBP4) resistant to PAPP-A cleavage, but retaining IGF-binding capacity, was used to block IGF activity in vivo. 4T1.2 mouse mammary adenocarcinoma cells transfected with empty vector, vector expressing wild-type IGFBP4 or vector expressing dBP4 were implanted in the mammary fat pad of BALB/c mice and tumour growth was assessed. Tumour angiogenesis and endothelial cell apoptosis were assessed by immunohistochemistry. RESULTS: 4T1.2 cells expressed the IGF1R receptor and IGFBP4. PAPP-A was expressed within mammary tumours but not by 4T1.2 cells. Proliferation and vascular endothelial growth factor (VEGF) production by 4T1.2 cells was increased by IGF1(E3R) (recombinant IGF1 resistant to binding by IGFBPs) but not by wild-type IGF1. IGF1-stimulated microvascular endothelial cell proliferation was blocked by recombinant IGFBP4. 4T1.2 tumours expressing dBP4 grew significantly more slowly than controls or tumours expressing wild-type IGFBP4. Inhibition of tumour growth by dBP4 was accompanied by the increased endothelial cell apoptosis. CONCLUSION: Protease-resistant IGFBP4 blocks IGF activity, tumour growth and angiogenesis.

Cellular senescence induced by aberrant MAD2 levels impacts on paclitaxel responsiveness in vitro.

BACKGROUND: The mitotic arrest deficiency protein 2 (MAD2) is a key component of the mitotic spindle assembly checkpoint, monitoring accurate chromosomal alignment at the metaphase plate before mitosis. MAD2 also has a function in cellular senescence and in a cell's response to microtubule inhibitory (MI) chemotherapy exemplified by paclitaxel. METHODS: Using an siRNA approach, the impact of MAD2 down-regulation on cellular senescence and paclitaxel responsiveness was investigated. The endpoints of senescence, cell viability, migration, cytokine expression, cell cycle analysis and anaphase bridge scoring were carried out using standard approaches. RESULTS: We show that MAD2 down-regulation induces premature senescence in the MCF7 breast epithelial cancer cell line. These MAD2-depleted (MAD2) cells are also significantly replicative incompetent but retain viability. Moreover, they show significantly higher levels of anaphase bridges and polyploidy compared to controls. In addition, these cells secrete higher levels of IL-6 and IL-8 representing key components of the senescence-associated secretory phenotype (SASP) with the ability to impact on neighbouring cells. In support of this, MAD2 cells show enhanced migratory ability. At 72 h after paclitaxel, MAD2 cells show a significant further induction of senescence compared with paclitaxel naive controls. In addition, there are significantly more viable cells in the MAD2 MCF7 cell line after paclitaxel reflecting the observed increase in senescence. CONCLUSION: Considering that paclitaxel targets actively dividing cells, these senescent cells will evade cytotoxic kill. In conclusion, compromised MAD2 levels induce a population of senescent cells resistant to paclitaxel.

Severe bone demineralisation is associated with higher mortality in children with cystic fibrosis.

Decreased bone mineral density (BMD) is an emerging problem for clinicians who care for children with Cystic fibrosis (CF). The aim of this study was to determine prevalence and assess risk factors for reduced BMD in our adolescent population with CF. All bone densitometry scans (n=99) performed on children (n=79) with a mean age 13.6 (10-19.2) years over a 7 year period (2000-2007) were reviewed. Patient records were reviewed for correlating clinical data. Low BMD is frequently present in adults and children with variable reports (36-66%). In our study, BMD expressed as z score of L2-L4 spine was reduced in a total of 50% children with a preponderance of males. Bone demineralization was strongly associated with increasing age (p=0.03), diminished lung function (p=0.027), reduced body mass index (p=0.001) and treatment with oral corticosteroids (p=0.02).